NMN and other components

Abstract

To provide a muscle enhancing composition and a muscle mass increasing composition enhancing muscle or increasing muscle mass which are necessary for a sport competition and labor, and for maintaining motion of walking, standing or the like in a daily life.SOLUTION: The invention is completed by finding that the problem is solved by taking in leucine and NMN.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a muscle-strengthening composition, a muscle mass-increasing composition, such as a pharmaceutical product, a health supplement, a feed, or a feed additive for muscle strengthening or muscle mass increase.

Background Art

[0002] In recent years, with the development of transportation means and the development of information and communication technologies, there is a lack of exercise. Further, in the elderly, a decrease in muscle mass is observed due to the influence of aging. However, generally, it may be difficult for the elderly to perform sufficient exercise to enhance muscle mass. The elderly generally have a small muscle mass, and in order to live safely, it may be desirable to enhance muscle mass and suppress muscle mass decline. Also, not only the elderly but also sports players may use pharmaceuticals or supplements when supplying necessary nutrients for enhancing necessary muscles.

[0003] To prevent muscle fatigue and strengthen muscles, branched-chain amino acids such as valine, leucine, and isoleucine are ingested. These are known to efficiently prevent muscle fatigue by inoculating branched-chain amino acids especially during exercise.

[0004] Furthermore, β-Nicotinamide mononucleotide (β-NMN) is an intermediate metabolite of β-Nicotinamide adenine dinucleotide (NAD), a metabolite in the de novo and Salvage pathways in living organisms (Patent Documents 1-4, Non-Patent Document 1). When administered to living organisms, β-NMN can directly induce NAD biosynthesis and increase NAD concentration in tissues (Non-Patent Document 2). Functions involving β-NMN have been reported, including "improvement of glucose metabolism abnormalities (Non-Patent Literature 2)," "involvement in circadianism (Non-Patent Literature 3, 4)," "improvement of aging mitochondrial function (Non-Patent Literature 5)," "protection of the heart from ischemia-reperfusion (Non-Patent Literature 6)," "suppression of the decrease in neural stem cells due to aging (Non-Patent Literature 7)," "suppression of Claudin-1 expression through epigenetic regulatory mechanisms and reduction of albuminuria in diabetic nephropathy (Non-Patent Literature 8)," "control of programmed cell death (Non-Patent Literature 9)," "improvement of Parkinson's disease (Non-Patent Literature 10)," and "recovery from oxidative stress and vascular dysfunction due to aging (Non-Patent Literature 11)." [Prior art documents] [Patent Documents]

[0005] [Patent Document 1] International release WO2014 / 146044 [Patent Document 2] Chinese Patent Gazette Registration No. 101601679 B [Patent Document 3] U.S. Patent Publication No. 2011-0123510 A1 [Patent Document 4] U.S. Patent Registration No. 7737158 [Non-patent literature]

[0006] [Non-Patent Document 1] Liana, R Stein . et al. The dynamic regulation of NADmetabolism in mitochondria. Trends in Endocrinology and Metabolism. 2012, Vol. 23, No. 9

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[0007] Against this backdrop, the present invention aims to provide a muscle-strengthening composition and a muscle-mass-increasing composition that strengthens or increases muscle mass necessary for sustaining movements such as walking and standing in sports competitions, work, and daily life. [Means for solving the problem]

[0008] As a result of diligent research to solve the above-mentioned problems, the inventors of this invention have found that the problems of the present invention can be solved by ingesting leucine and NMN, and have completed this invention. The present invention (1) A composition comprising β-nicotinamide mononucleotide or a pharmaceutically acceptable salt thereof, and solvates thereof, and leucine or a pharmaceutically acceptable salt thereof, and solvates thereof. (2) A muscle-building composition comprising β-nicotinamide mononucleotide or a pharmaceutically acceptable salt thereof, and solvates thereof, and leucine or a pharmaceutically acceptable salt thereof, and solvates thereof as active ingredients. (3) A health supplement containing the composition described in (1) or (2), which is taken to enhance muscle mass. (4) A feed containing the composition described in (1) or (2), which is ingested to enhance muscle, This relates to the matter. [Effects of the Invention]

[0009] The composition of the present invention can provide a composition for enhancing muscle, such as a pharmaceutical, a health supplement, or a feed, which has an effect of enhancing the muscles of animals including humans or increasing muscle mass. Further, the present invention can provide a method for enhancing the muscles of animals including humans, suppressing a decrease in muscle mass, or increasing muscle mass.

Brief Description of Drawings

[0010] [Figure 1] Results of Examples

Modes for Carrying Out the Invention

[0011] In the present invention, "enhancement of muscle" or "increase in muscle mass" mainly means increasing the muscle mass or muscle strength of skeletal muscle, and includes an increase in muscle weight and the like. Further, a decrease in muscle mass or muscle strength is called muscle atrophy, and the muscle enhancement referred to in the present invention also includes improvement of muscle atrophy.

[0012] In the present invention, "leucine" means an amino acid, which is L - leucine or its physiologically acceptable salt. There is no particular limitation on the leucine applicable in the present invention, and examples include those derived from natural sources, those chemically synthesized, or combinations thereof. Examples of commercially available L - leucine include L - leucine (manufactured by Kyowa Hakko Bio Co., Ltd.). Further, a composition containing leucine, such as yeast extract or protein hydrolysate, may also be used.

[0013] In the present invention, there are no particular limitations on the applicable "β-Nicotinamide mononucleotide (β-NMN)". There are also no limitations on the method of preparing β-NMN. For example, β-NMN obtained by chemical synthesis, enzymatic methods, fermentation, etc., and purified can be used as the active ingredient. Furthermore, since β-NMN is a component that is widely present in living organisms, β-NMN obtained by extraction and purification from natural raw materials such as animals, plants, and microorganisms can also be used as the active ingredient. Commercially available β-NMN may also be used. A composition containing β-NMN, such as yeast extract, may also be used.

[0014] In the present invention, leucine and β-NMN may be pharmaceutically acceptable salts of inorganic salts or organic salts having a basic moiety such as an amine. Examples of acids that constitute such salts include acetic acid, benzenesulfonic acid, benzoic acid, camphorsulfonic acid, citric acid, ethensulfonic acid, fumaric acid, gluconic acid, glutamic acid, hydrobromic acid, hydrochloric acid, isethionic acid, lactic acid, maleic acid, malic acid, mandelic acid, methanesulfonic acid, mucinic acid, nitric acid, pamoic acid, pantothenic acid, phosphoric acid, succinic acid, sulfuric acid, tartaric acid, and p-toluenesulfonic acid. They may also be alkali salts or organic salts having an acidic moiety such as a carboxylic acid. Examples of bases that constitute such salts include alkali metal salts or alkaline earth metal salts derived from bases such as sodium hydride, potassium hydroxide, calcium hydroxide, aluminum hydroxide, lithium hydroxide, magnesium hydroxide, zinc hydroxide, ammonia, trimethylammonia, triethylammonia, ethylenediamine, lysine, arginine, ornithine, choline, N,N'-dibenzylethylenediamine, chloroprocaine, procaine, diethanolamine, N-benzylphenethylamine, diethylamine, piperazine, tris(hydroxymethyl)-aminomethane, and tetramethylammonium hydroxide.

[0015] In this invention, there are no restrictions on the method of mixing leucine and β-NMN; any general method is acceptable. They may be mixed in powder form, or they may be mixed after being dissolved or dispersed in water or the like. Furthermore, the mixing ratio is arbitrary and unrestricted.

[0016] In the present invention, other active ingredients may be included in addition to leucine and β-NMN. These other active ingredients are not particularly limited as long as they do not impair the effects of the present invention. Examples of such other active ingredients include compositions known to have muscle-building effects. Specifically, examples of such other active ingredients include branched-chain amino acids other than leucine, whey protein, catechins, etc. Furthermore, various components mixed in other supplements and pharmaceuticals may be included as long as they do not impair the effects of the present invention. Examples include amino acids, taurine, glutathione, carnitine, creatine, coenzyme Q, glucuronic acid, glucuronolactone, capsicum extract, ginger extract, cocoa extract, guarana extract, garcinia extract, theanine, γ-aminobutyric acid, capsaicin, capsiate, various organic acids, flavonoids, polyphenols, catechins, xanthine derivatives, indigestible oligosaccharides such as fructooligosaccharides, and polyvinylpyrrolidone.

[0017] In the present invention, the active ingredient can be combined with a non-toxic pharmaceutical carrier and formulated into various dosage forms using conventional formulation methods. Among the dosage forms of the secretion-enhancing agent according to the present invention, oral preparations include, for example, solid preparations such as tablets, granules, powders, capsules, and soft capsules; liquid preparations such as solutions, suspensions, and emulsions; and lyophilized preparations. Parenteral preparations include injections, as well as suppositories, sprays, and transdermal preparations.

[0018] Examples of non-toxic pharmaceutical carriers used in formulation include sugars such as glucose, lactose, sucrose, fructose, and reduced maltose; carbohydrates such as starch, hydroxyethyl starch, dextrin, β-cyclodextrin, crystalline cellulose, and hydroxypropyl cellulose; sugar alcohols such as mannitol, erythritol, sorbitol, and xylitol; esters such as fatty acid glycerides and polyoxyethylene sorbitan fatty acid esters; polyethylene glycol, ethylene glycol, amino acids, albumin, casein, silicon dioxide, water, and physiological saline. Furthermore, in the formulation of the secretion-enhancing agent according to the present invention, conventional additives such as stabilizers, lubricants, wetting agents, emulsifiers, suspending agents, binders, disintegrants, solvents, solubilizers, buffers, isotonic agents, preservatives, flavoring agents, and colorants may be added as needed in the formulation.

[0019] The present invention is preferably administered to humans and non-human animals. There are no particular restrictions on non-human animals, but livestock, pets, and other animals can be considered.

[0020] The dosage of the composition of the present invention is appropriately selected and determined based on the species, age (in months), weight, symptoms, severity of the disease, administration schedule, and formulation form of the animal to be administered. For example, the daily dose for one adult can be 0.1 mg to 10 g, preferably 0.5 mg to 7 g, more preferably 10 mg to 5 g, and even more preferably 100 mg to 2 g of β-NMN, administered in one dose or in several divided doses. Similarly, the amount of leucine can be appropriately selected and determined based on the species, age (in months), weight, symptoms, severity of the disease, administration schedule, and formulation form of the animal to be administered. For example, the daily dose for one adult can be 0.1 mg to 10 g, preferably 0.5 mg to 7 g, more preferably 10 mg to 5 g, and even more preferably 100 mg to 2 g of leucine, administered in one dose or in several divided doses.

[0021] The leucine and β-NMN of the present invention are biological components and are also found in food, and are therefore considered to be highly safe. Thus, the composition of the present invention can be used as an active ingredient in health supplements. Health supplements are intended to supplement nutrition for the purpose of maintaining or improving health, and include foods for specified health uses and foods with nutritional function claims. The composition of the present invention can also be incorporated into animal feed for purposes such as maintaining animal health and used as a health supplement feed.

[0022] The health supplements and feeds according to the present invention may contain other food ingredients and various additives. Examples of food ingredients include vitamins, carbohydrates, proteins, lipids, dietary fiber, and fruit juice. Specifically, examples include B vitamins such as vitamin B1 derivatives, vitamin B2, vitamin B6, vitamin B12, vitamin B13, biotin, pantothenic acid, nicotinic acid, and folic acid; fat-soluble vitamins such as vitamin E, vitamin D or its derivatives, vitamin K1, vitamin K2, and beta-carotene; minerals such as calcium, potassium, iron, and zinc; yeast, L-carnitine, creatine, alpha-lipoic acid, glutathione, glucuronic acid, taurine, collagen, soy isoflavones, lecithin, peptides, amino acids, gamma-aminobutyric acid, diacylglycerol, DHA, EPA, capsaicin, chondroitin sulfate, Agaricus mushroom extract, carrot extract, garlic extract, green juice, lecithin, royal jelly, propolis, octacosanol, flavangenol, pycnogenol, maca, chitosan, garcinia extract, chondroitin, and glucosamine. Additives include sweeteners, acidulants such as organic acids, stabilizers, flavorings, and colorings.

[0023] The health supplements and feeds according to the present invention can be manufactured by adding appropriate additives to leucine, β-NMN, etc., and then forming them into a form suitable for consumption, such as powder, granules, tablets, capsules, soft capsules, or paste, using conventional means. The health supplements according to the present invention may be consumed as is, or they may be consumed after being mixed with various foods and beverages. For example, powdered health supplements can be consumed after being dissolved or dispersed in beverages such as water, alcoholic beverages, fruit juice, milk, or soft drinks. The feeds according to the present invention may also be consumed by animals as is, or they may be consumed after being mixed with other solid feeds or drinking water. [Examples]

[0024] The present invention will be described in more detail below based on examples. However, the present invention is not limited to the following examples. All animal experiments were conducted on the University of Tokyo campus in accordance with the guidelines of the University of Tokyo's Animal Experimentation Committee.

[0025] For two months, aged mice (C57B6 / J, 80 weeks old, male, n=3) were administered control, 1.5% by weight L-leucine (1500 mg / kg BW), NMN (500 mg / kg BW), and 1.5% by weight L-leucine (1500 mg / kg BW) + NMN (500 mg / kg BW) drinking water ad libitum. Skeletal muscle was then collected and muscle weight was evaluated. The mice were given a body weight of 30 g and a daily water intake of 3 mL.

[0026] The results are shown in Figure 1. Only the group of mice that received both leucine and NMN showed an increase in muscle mass. [Industrial applicability]

[0027] As detailed above, the present invention provides a muscle-enhancing or muscle-mass-increasing composition effective for strengthening the muscles of humans and non-human animals. Furthermore, the present invention provides an effective method for strengthening the muscles or increasing the muscle mass of humans and non-human animals.

Claims

1. A muscle-building composition comprising β-nicotinamide mononucleotide or a pharmacoagulably acceptable salt thereof, and solvates thereof, and leucine or a pharmacoagulably acceptable salt thereof, and solvates thereof as active ingredients.

2. A health supplement containing the composition described in claim 1, which is taken to enhance muscle mass.

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